The present invention relates to methods, compounds, compositions and kits useful for delivering to a target site a targeting moiety that is conjugated to one member of a ligand/anti-ligand pair. After localization and clearance of the targeting moiety conjugate, direct or indirect binding of a diagnostic or therapeutic agent conjugate at the target site occurs. Methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as the related compounds, are also disclosed.
The present invention describes three-step pretargeting diagnostic and therapeutic methods. Three-step pretargeting protocols feature administration of a targeting moiety-ligand conjugate, which is allowed to localize at a target site and to dilute in the circulation. Subsequently administered anti-ligand binds to the targeting moiety-ligand conjugate in both blood and at a target site and clears unbound antibody-ligand conjugate from the blood. A diagnostic or therapeutic agent-ligand conjugate that exhibits rapid whole body clearance is then administered and binds to the targeting moiety-ligand-anti-ligand localized at a target site, thereby constituting the third target site-localized component in the protocol.
Preferred three-step pretargeting methods of the present invention employ biotin/avidin as the ligand/anti-ligand binding pair. These preferred three-step pretargeting methods involve the administration of biotin conjugated to therapeutic or diagnostic radionuclides or other active agents such as chemotherapeutic drugs, anti-tumor agents such as cytokines and the like. Y-90-DOTA-biotin conjugates are particularly preferred in the practice of the present invention.